This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. These studies examine the functional interactions and the anatomy of the connections between the intralaminar nuclei of the thalamus (i.e., the centromedian and parafascicular nuclei (CM/PF)) and the striatum in normal and parkinsonian monkeys. Projections from the CM to the putamen terminate preferentially on cholinergic striatal interneurons which may then shape striatal output under normal and pathologic conditions. We have found that electrical CM stimulation with short trains of stimuli results in complex sequences of activation and inhibition in striatal cells, most likely through intrastriatal spread of activity and processing through local inhibitory axon collaterals and cholinergic interneurons. As the inhibitory stimulation responses may be mediated by GABAergic intrinsic striatal neurons, we are examining the termination patterns of axon collaterals of such GABAergic neurons onto cholinergic neurons. We found that a large proportion of these axon collaterals indeed terminates on the cholinergic interneurons. We also continued with our studies of the electrophysiologic responses of striatal neurons to CM stimulation in two animals. At least a subset of such responses can be blocked in our experiments by glutamatergic or GABAergic drugs, but not by acetylcholine receptor blockers. Finally, we have begun to study changes in the number of neurons in the intralaminar nuclei in parkinsonian (MPTP-treated) monkeys. These studies (thus far in 1 control, and 4 MPTP-treated monkeys) show that MPTP-treatment leads to a 55-60% reduction of neurons in the intralaminar nuclei. Loss of such neurons may have a major impact on striatal functioning in parkinsonism.